Despite considerable progress in diagnosing and treating solid tumors, metastatic disease remains the foremost cause of cancer-related death. While metastasis is widely considered as a late event in the evolution of malignant tumors, cells can disseminate from tumors in even the earliest stages of cancer progression. See e.g. Weinberg, Cancer Cell 14(4):283 (2008); Podsypanina et al., Science 321(5897):1841 (2008); Riethmüller et al., Cancer Cell 13(1):58 (2008). Although the mechanisms of metastasis development are yet to be fully elucidated, circulation of tumor cells within the blood is considered a fundamental intermediate event in the metastatic cascade. In addition, disseminated tumor cells (“DTC”) are believed to home to the bone marrow in various solid tumors of epithelial origin and the bone marrow thus becomes an occult reservoir of tumor cells.
With current diagnostic approaches, the spread of tumor cells in most patients is undetected until after metastatic disease is well-established, and early, potentially effective, intervention is not an option. In addition, most therapeutic decisions are presently informed by metrics that mainly reflect the nature of the primary tumor. See Fischer, Arch. Pathol. Lab. Med. 133(9):1367 (2009). However, as evidenced by therapeutic resistance, tumor genotype and phenotype often change over the course of treatment. Circulating tumor cells (“CTC”) function as immediate indicators of tumor load and character, and evaluation of CTCs provides real-time information regarding treatment efficacy. See Mostert et al., Cancer Treat. Rev 35(5):463 (2009). Introduction of a facile means for the early detection and continual systemic monitoring of circulating tumor cells would allow timely administration of a wider range of treatment options that are more appropriately tailored to a patient's specific disease as indicated by the changing characteristics of both the primary tumor, and just as importantly, nascent metastases.